Dataset Information

Temporal and Spatial Heterogeneity of Host Response to SARS-CoV-2 Pulmonary Infection [gene expression]

ABSTRACT: The relationship of SARS-CoV-2 lung infection and severity of pulmonary disease is not fully understood. We analyzed specimens from 24 autopsies from patients who succumbed to SARS-CoV-2 infection using a combination of different RNA and protein analytical platforms to characterize inter- and intra- patient heterogeneity of pulmonary virus infection. There was a spectrum of high and low virus cases that was associated with duration of disease and activation of interferon pathway genes. Using a digital spatial profiling platform, the intra-pulmonary spatial heterogeneity of the virus corresponded to focal expression of interferon response genes and association with immune checkpoint genes In this dataset, we capture the GeoMx DSP RNA profiling work done in conjunction with this study. The files here represent SARS-CoV-2 infected rapid autopsy patients (n = 6) which were profiled with the NanoString GeoMx COVID19 Atlas RNA panel v1.0. This panel was then read out using Illumina sequencing following standard library preparation according to manufacturer protocols. Attached below are low-resolution images of each slide with placement of all ROIs, as well as individual images of each ROI, segments, and UV illuminated IF channels. For access to high resolution (single channel, composite, or ROI) images please contact GeoMxSupport@nanostring.com or the corresponding author of the study. RNA sequencing data and results for bulk RNA profiling can be accessed in study GSE150316.

ORGANISM(S): Severe acute respiratory syndrome coronavirus 2 Homo sapiens

PROVIDER: GSE159787 | GEO | 2020/11/14

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:SARS-CoV-2 primarily affects the respiratory system but extra-pulmonary manifestations in individuals with COVID-19 are commonly seen. All major organ systems have been reported to be affected by SARS-CoV-2 and complications arising from ensuing organ dysfunction significantly increase the mortality rate of COVID-19. Yet, despite the clinical importance of systemic involvement of SARS-CoV-2, little is known about the pathogenesis of extra-pulmonary complications of COVID-19. Here, we create a murine model of SARS-CoV-2 induced severe systemic toxicity and multi- organ involvement by expressing the human ACE2 transgene in multiple tissues using an adeno associated virus (serotype 9) followed by administration of the SARS-CoV-2 virus intra-peritoneally. The animals develop a profound phenotype within 7 days of SARS-CoV-2 infection with severe weight loss, morbidity and failure to thrive, that necessitated euthanasia. We demonstrate that following a robust anti-viral immune response, there is metabolic suppression of oxidative phosphorylation and the tri- carboxylic acid (TCA) cycle in multiple organs with neutrophilia, lymphopenia and splenic atrophy mirroring human COVID-19 phenotypes with adverse prognosis. Animals had a significantly lower heart rate and electron microscopy demonstrated myofibrillar disarray and myocardial edema, a common pathogenic cardiac phenotype in human COVID-19. An organ wide metabolic reprogramming consistent with depression of oxidative phosphorylation led to utilization of peripheral fat stores and gross accumulation of fat in the heart and other vital organs. We perform metabolomic profiling of peripheral blood and identify a panel of TCA cycle metabolites that serve as biomarkers of depressed oxidative phosphorylation, several of these markers been noted in human clinical studies to be associated with adverse prognosis. Finally, we observed that SARS-CoV-2 induces epigenetic changes with a significant number of differentially methylated sites in vital organs, across the whole host cell genome, that affects expression of immune response genes and could in part contribute to dysregulated gene expression in affected tissues. Our model suggests that SARS-CoV- 2 induced metabolic reprogramming and epigenetic changes in internal organs could contribute to systemic toxicity and lethality in COVID-19.

Dataset Information

Temporal and Spatial Heterogeneity of Host Response to SARS-CoV-2 Pulmonary Infection [gene expression]

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets